ACSF2-mediated ferroptosis is involved in ulcerative colitis

Abstract

AimsTo investigate the role of ferroptosis-related genes in the induction into ulcerative colitis (UC) and provide new strategies for the prevention and treatment of UC. Materials and methodsWe screened the UC dataset from the GEO database and obtained ferroptosis-related genes from FerrDB and GeneCards. The R package “CancerSubtypes” was performed to identify the UC subtypes, followed by Short Time-series Expression Miner (STEM) analysis. The key genes were further screened by machine learning algorithms (LASSO and SVM-RFE). WB and IHC verified the changes in the expression content of ACSF2 in vivo and in vitro models. The changes in intracellular ROS and Fe2 + levels were detected. Key findingsThrough bioinformatics analysis, we selected the ferroptosis-related gene ACSF2 (acyl CoA synthetase family member 2), which is significantly associated with immune-related pathways “Toll-like receptor signaling pathway”, “NF-kappa B signaling pathway” and “NOD-like receptor signaling pathway”. The expression of ACSF2 was significantly down-regulated in UC animals, Salmonella typhimurium colitis models and cell models, while the ferroptosis inhibitor Fer-1 reversed the expression of ACSF2 in LPS-induced cell models, indicating that the ferroptosis-related gene ACSF2 plays an important role in mediating ferroptosis and inflammation, and is expected to become a new target for further research. SignificanceFerroptosis is closely associated with the development of UC, and the ferroptosis-related gene ACSF2 can be used as a potential biomarker for the diagnosis and treatment of UC.